Inhibin and activin proteins are best known for their role as endocrine regulators of FSH synthesis and release. In addition to their endocrine role, these proteins may also function as transsynapic mediators in the brain, serve as paracrine and autocrine modulators of reproductive functions, and affect the growth and differentiation of a number of cell types. While these effects have been demonstrated in vitro, or in mature animals, very little is known about the function of inhibin and activin during normal fetal and postnatal development. The long-range objectives of this research are to fully understand the mechanisms by which inhibin and activin regulate normal human embryogenesis and serve as endocrine, paracrine, autocrine, and interneuronal communicators in the developing fetus and throughout postnatal maturation. Knowledge of the roles of inhibin and activin, as hormones and growth factors in normal systems, is fundamental to understanding and treating abnormalities, such as birth defects and reproductive disorders, involving these factors. The short-- term goals of the proposed research are to establish the basis for this understanding by answering some specific questions concerning the spatiotemporal localization, regulation, and sites of action of inhibin and activin proteins, and mRNAs, during normal rat and human embryogenesis and in the developing rat and human hypothalamic-pituitary-gonadal axis. The ontogeny of the spatiotemporal distribution of message encoding inhibin/activin subunits, an activin binding protein, and activin receptor will be studied in the rat and human fetus, and in rat and human gonads, pituitary, and brain, from birth to adulthood using a well characterized in situ hybridization procedure. Spatiotemporal localizations of the proteins will be examined in these tissues using established immunohistochemical techniques. Immunofluorescence will be used to determine subunit and binding protein co-localizations and to identify cell types containing these proteins. The more sensitive avitin-biotinylated horseradish peroxidase procedure will be used for screening areas of low abundance and will provide more permanent staining. Levels of output of mRNA expression will be measured using quantitative Sl-nuclease protection analysis.